Hypothyroidism — Med2Date

📋 Key Information Summary

📋

Hypothyroidism is a deficiency of thyroid hormones (T3 and T4) resulting from impaired thyroid gland function (primary) or hypothalamic–pituitary dysfunction (secondary/central).
Hashimoto's thyroiditis (chronic autoimmune thyroiditis) is the most common cause in iodine-replete populations such as Australia.
The hallmark biochemical finding is an elevated serum TSH with low free T4 (FT4) in primary hypothyroidism; secondary hypothyroidism presents with low or inappropriately normal TSH and low FT4.
Levothyroxine (L-T4) is the standard replacement therapy — e.g., Oroxine®, Eutroxsig® — initiated at 1.6 µg/kg/day in healthy young adults; lower starting doses in the elderly and cardiac disease.
TSH should be measured 6–8 weeks after initiation or dose change, then every 6–12 months once stable; target TSH typically 0.4–4.0 mIU/L.
Levothyroxine must be taken on an empty stomach 30–60 minutes before breakfast; concurrent calcium, iron, and PPIs impair absorption and require dose adjustment.
Subclinical hypothyroidism (elevated TSH, normal FT4) is common; treatment is recommended when TSH >10 mIU/L or TSH 5–10 mIU/L with symptoms, positive TPO antibodies, or pregnancy intent.
In pregnancy, the TSH upper reference limit is lower (trimester-specific); untreated hypothyroidism increases risk of miscarriage, pre-eclampsia, and impaired neurodevelopment.
Myxoedema coma is a rare, life-threatening emergency requiring IV levothyroxine, IV hydrocortisone, ICU admission, and management of hypothermia and hyponatraemia.
Aboriginal and Torres Strait Islander peoples have higher rates of autoimmune disease; screening and access to thyroid function testing in remote communities must be prioritised.
Levothyroxine (Oroxine®, Eutroxsig®, generic L-T4) is PBS-listed as a General Benefit — no Authority required.

🎧 Audio Brief

The Delicate Seesaw of Thyroid Health

A short clinical audio briefing generated from this article — perfect for the commute or ward round.

Introduction & Australian Epidemiology

Hypothyroidism is a common endocrine disorder characterised by deficient production or action of thyroid hormones — thyroxine (T4) and triiodothyronine (T3) — resulting in a global reduction of metabolic activity. It is classified as primary (thyroid gland failure, >95 % of cases) or secondary/central (pituitary or hypothalamic disease).

Australia is an iodine-replete nation following the mandatory iodisation of bread salt (2009), and the overall prevalence of overt hypothyroidism is approximately 1–2 %, with subclinical hypothyroidism affecting an additional 4–10 % of adults depending on assay cut-offs. Women are 5–8 times more likely to be affected than men, and prevalence rises sharply with age — reaching 10–15 % in women over 60 years.

Hashimoto's thyroiditis (chronic lymphocytic / autoimmune thyroiditis) is the single most common aetiology in Australia, followed by iatrogenic causes — radioiodine (I-131) therapy and thyroidectomy for Graves' disease or thyroid carcinoma. Less common causes include drug-induced hypothyroidism (amiodarone, lithium, immune checkpoint inhibitors), iodine deficiency or excess, infiltrative diseases, and congenital hypothyroidism (detected via the Australian Newborn Bloodspot Screening Programme).

Hypothyroidism is readily diagnosed with a single serum TSH measurement and is one of the most satisfying conditions in endocrinology to treat, with near-complete symptom resolution in the majority of patients on appropriate levothyroxine replacement. Nevertheless, persistent symptoms despite biochemically normal TSH levels remain a clinical challenge and necessitate careful re-evaluation of adherence, absorption, comorbidities, and patient expectations.

Aetiology & Pathophysiology

The thyroid gland produces T4 (the predominant secretory product) and smaller quantities of T3 (the biologically active hormone). Thyroid hormone synthesis is regulated by the hypothalamic–pituitary–thyroid (HPT) axis via TRH → TSH → thyroid hormone negative feedback.

Primary Hypothyroidism

Destruction or dysfunction of the thyroid gland leads to reduced T4/T3 output and loss of negative feedback, resulting in compensatory TSH elevation. Causes include:

Hashimoto's thyroiditis — the most common cause worldwide and in Australia. An autoimmune process mediated by CD4+ T-helper cells, anti-thyroid peroxidase (anti-TPO) antibodies, and anti-thyroglobulin (anti-Tg) antibodies. Lymphocytic infiltration gradually replaces functional thyroid tissue with fibrosis. Progression from euthyroidism → subclinical → overt hypothyroidism occurs at ~5 % per year in antibody-positive individuals.
Iatrogenic — radioiodine (I-131) ablation for Graves' disease or thyroid cancer (hypothyroidism develops in 50–80 % within 5–10 years); total thyroidectomy; external beam radiotherapy to the neck.
Drug-induced — amiodarone (type 2 amiodarone-induced thyroiditis or inhibition of 5'-deiodinase); lithium (inhibits thyroid hormone release); immune checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab — thyroiditis with subsequent hypothyroidism in 5–20 %); tyrosine kinase inhibitors (lenvatinib, sunitinib); interferon-α; interleukin-2.
Iodine deficiency — historically the leading cause globally; now uncommon in Australia due to mandatory iodisation programmes, but mild deficiency persists in some regions (e.g., parts of Tasmania, some Aboriginal and Torres Strait Islander communities).
Iodine excess — the Wolff–Chaikoff effect; excess iodine transiently inhibits thyroid hormone synthesis. Relevant in patients receiving iodinated contrast, amiodarone, or Lugol's iodine.
Infiltrative diseases — amyloidosis, sarcoidosis, haemochromatosis, Riedel's thyroiditis, Langerhans cell histiocytosis.
Congenital — thyroid dysgenesis (agenesis, ectopy) accounts for ~85 %; dyshormonogenesis (inborn errors of thyroid hormone synthesis) ~15 %. Detected by the Australian Newborn Bloodspot Screening Programme (heel-prick TSH at 48–72 hours).

Secondary (Central) Hypothyroidism

Caused by insufficient TSH secretion from the pituitary or TRH from the hypothalamus. Causes include pituitary adenomas, craniopharyngiomas, pituitary surgery or radiotherapy, Sheehan syndrome, lymphocytic hypophysitis, sarcoidosis, and haemochromatosis. Key diagnostic feature: low or inappropriately normal TSH with low FT4 — TSH is not a reliable marker for monitoring replacement in these patients.

Subclinical Hypothyroidism

Defined biochemically as elevated TSH (typically 4.5–10 mIU/L) with normal FT4. Represents early thyroid failure. Most patients are asymptomatic or have non-specific symptoms. Approximately 2–5 % progress to overt hypothyroidism annually, particularly if TPO-antibody positive. Management remains controversial; treatment is generally recommended when TSH >10 mIU/L or with symptoms, positive antibodies, pregnancy planning, or cardiovascular risk factors.

⚠️

Central hypothyroidism pitfall: Never rely on TSH alone to diagnose or monitor central hypothyroidism. Always measure FT4 directly. In suspected pituitary disease, assess the full pituitary hormone axis before initiating replacement.

Clinical Features

The clinical presentation of hypothyroidism is insidious and often non-specific, leading to delayed diagnosis. Symptoms correlate with the degree and duration of thyroid hormone deficiency and the patient's age. Many features are absent in mild or subclinical disease.

Common Symptoms

System	Symptoms & Signs
Constitutional	Fatigue, lethargy, cold intolerance, weight gain (usually modest, 2–5 kg), hypothermia
Dermatological	Dry skin, coarse hair, hair loss (including lateral third of eyebrows — Queen Anne sign), brittle nails, myxoedema (non-pitting oedema of skin, especially periorbital)
Cardiovascular	Bradycardia, diastolic hypertension, pericardial effusion, elevated LDL cholesterol, accelerated atherosclerosis
Neuropsychiatric	Cognitive slowing, poor concentration, depression, carpal tunnel syndrome, delayed deep tendon reflexes (prolonged relaxation phase)
Gastrointestinal	Constipation, reduced appetite
Musculoskeletal	Myalgia, arthralgia, proximal muscle weakness, elevated CK
Reproductive	Menorrhagia, oligomenorrhoea, infertility, erectile dysfunction, hyperprolactinaemia (galactorrhoea)
Haematological	Macrocytic or normocytic anaemia
ENT	Goitre (Hashimoto's), hoarse voice, macroglossia

Myxoedema Coma

Myxoedema coma is a rare but life-threatening decompensation of severe, untreated hypothyroidism with a mortality rate of 25–60 %. It typically occurs in elderly patients with longstanding undiagnosed hypothyroidism, precipitated by infection, surgery, cold exposure, sedatives, or medication non-adherence.

🚨

Myxoedema coma — emergency features:

Profound hypothermia (<35 °C)
Altered consciousness — confusion → stupor → coma
Severe bradycardia, hypotension
Hypoventilation with respiratory failure (CO₂ retention)
Hyponatraemia (dilutional, impaired free water excretion)
Hypoglycaemia

Requires immediate ICU admission, IV levothyroxine, IV hydrocortisone (to prevent adrenal crisis), passive rewarming, and supportive care.

Investigations & Diagnosis

Diagnosis of primary hypothyroidism is biochemical, centred on serum TSH and FT4. Clinical history, examination, and antibody testing assist in determining the aetiology.

First-Line Investigations

Essential

Serum TSH

The single most sensitive screening test. MBS Item 66716. Elevated in primary hypothyroidism; low/normal in central hypothyroidism. Reference range: 0.4–4.0 mIU/L (lab-specific).

Essential

Free T4 (FT4)

MBS Item 66715. Low in overt hypothyroidism; normal in subclinical hypothyroidism. Always request when TSH is abnormal. Essential for monitoring central hypothyroidism.

Available

Free T3 (FT3)

MBS Item 66717. Not routinely required for diagnosis. May be useful in central hypothyroidism or suspected euthyroid sick syndrome. Often normal until hypothyroidism is severe.

Available

Anti-TPO antibodies

MBS Item 66800. Positive in ~90 % of Hashimoto's thyroiditis. Useful to confirm autoimmune aetiology and predict progression from subclinical to overt hypothyroidism. Medicare-rebatable.

Available

Anti-thyroglobulin (anti-Tg) antibodies

MBS Item 66801. Positive in ~60–80 % of Hashimoto's. Less specific than anti-TPO; add if anti-TPO negative but Hashimoto's suspected.

Diagnostic Interpretation

Pattern	TSH	FT4	Interpretation
Overt primary hypothyroidism	↑↑ (typically >10)	↓	Confirmed; treat with levothyroxine
Subclinical hypothyroidism	↑ (4.5–10)	Normal	Consider treatment if TPO+, symptomatic, or TSH >10
Central hypothyroidism	Low or inappropriately normal	↓	Suspect pituitary/hypothalamic pathology; MRI pituitary
Isolated TSH elevation	Mildly ↑	Normal	Repeat in 6–8 weeks; consider assay interference, heterophilic antibodies, macro-TSH

Additional Investigations

Thyroid ultrasound: Not routinely required for diagnosis. Indicated if goitre, palpable nodule, or asymmetric thyroid enlargement. Features of Hashimoto's include diffuse hypoechogenicity, heterogeneous echotexture, and fibrous septations.
FBC: Normocytic or macrocytic anaemia.
Lipid profile: Hypercholesterolaemia (↑ LDL) and occasionally hypertriglyceridaemia. Should improve with adequate replacement.
Serum CK: Often elevated (2–10× normal) in overt hypothyroidism — a common source of unnecessary investigation for myopathy.
Sodium: Hyponatraemia (dilutional) may be present.
Prolactin: Mildly elevated due to TRH stimulation of lactotrophs. Galactorrhoea may occur.
MRI pituitary: Required if central hypothyroidism suspected to exclude structural lesion.

⚠️

Screening: Universal screening for hypothyroidism is not recommended in Australia (RACGP / RCPA position). Targeted testing is appropriate in patients with symptoms, goitre, personal or family history of autoimmune thyroid disease, type 1 diabetes mellitus, coeliac disease, other autoimmune conditions, hyperlipidaemia unresponsive to treatment, pregnancy planning or early pregnancy, Down syndrome, or Turner syndrome.

Management (Levothyroxine)

Levothyroxine (L-T4, synthetic thyroxine) is the standard and preferred replacement therapy for all forms of hypothyroidism. It is a prohormone that undergoes peripheral conversion to the active T3 by type 1 and type 2 deiodinases. T3 supplementation (liothyronine) is not routinely recommended and is not PBS-listed in Australia.

Levothyroxine Dosing

💊

Levothyroxine Sodium (L-T4)

Oroxine® · Eutroxsig® · Generic · Synthetic T4

Adult dose Full replacement: 1.6 µg/kg/day PO (lean body weight). Typical: 75–150 µg once daily.

Starting dose — healthy adults <60 yr Full replacement dose (1.6 µg/kg/day) — can start at full dose in young, otherwise healthy patients.

Starting dose — elderly or cardiac 25–50 µg/day; increase by 25 µg every 4–6 weeks. Avoid rapid dose escalation — risk of angina, MI, arrhythmias.

Route Oral — on empty stomach, 30–60 min before breakfast. Consistent timing is critical.

Frequency Once daily. If missed dose, take as soon as remembered; do not double dose.

Renal adjustment No dose adjustment required for renal impairment.

Hepatic adjustment No dose adjustment; however, severe liver disease may alter T4–T3 conversion.

Paediatric dose Congenital hypothyroidism: 10–15 µg/kg/day neonates; 4–6 µg/kg/day children 1–5 yr; 2–4 µg/kg/day children >5 yr. Initiate urgently — within 1–2 weeks of newborn screening result.

PBS status ✔ PBS General Benefit

Administration Guidance

⚠️

Absorption interactions — advise patients:

Take levothyroxine 30–60 minutes before breakfast, on an empty stomach, with water only.
Separate by ≥4 hours from: calcium supplements, iron tablets, antacids (Mg/Al), sucralfate, cholestyramine, PPIs (esomeprazole, omeprazole — raise gastric pH and reduce absorption).
Soy-based infant formula and high-fibre diets may reduce absorption.
Consistency matters — patients who eat breakfast immediately after dosing should do so consistently; the dose can be titrated to achieve target TSH with this pattern.
Bedtime dosing (≥3 hours after last meal) is an acceptable alternative if morning adherence is poor — some studies suggest comparable or superior absorption.

Monitoring After Initiation

Re-check TSH at 6–8 weeks after starting or changing dose. Adjust by 12.5–25 µg increments.
Target TSH: 0.4–4.0 mIU/L for most adults. In younger patients, aim for the lower half of the reference range (0.4–2.5 mIU/L) for optimal well-being.
Once stable: Check TSH annually (or more frequently if symptoms change, weight alters significantly, or new interacting medications introduced).
Overtreatment: Suppressing TSH <0.1 mIU/L in non-cancer patients increases risk of atrial fibrillation (especially elderly) and osteoporosis (especially postmenopausal women). Avoid.
Do not use FT4 alone for monitoring — TSH is the most sensitive marker in primary hypothyroidism.

Persistent Symptoms Despite Normal TSH

A subset of patients (10–15 %) report persistent fatigue, cognitive difficulty, or weight gain despite TSH within target range. Management approach:

Reassess adherence and administration technique.
Investigate comorbidities: iron deficiency, vitamin D deficiency, coeliac disease, depression, sleep apnoea, chronic fatigue syndrome.
Check FT4 and FT3 — consider whether FT3 is low-normal (some patients have impaired deiodinase conversion; combination T4/T3 therapy is not routinely recommended but may be trialled under specialist endocrinology guidance).
Set realistic expectations — some symptoms may be unrelated to thyroid status.
Refer to endocrinology if refractory.

Subclinical Hypothyroidism — Treatment Decision

Observation

TSH 4.5–10, asymptomatic, TPO-negative

Repeat TSH in 6–12 months. Monitor for symptom development. No treatment required.

Setting: GP follow-up

Consider treatment

TSH 4.5–10 with symptoms, TPO+, or cardiovascular risk

A therapeutic trial of levothyroxine (25–50 µg/day) is reasonable. Reassess symptoms and TSH at 3 months. Discontinue if no benefit.

Setting: GP with trial and review

Treat

TSH >10 mIU/L

Treatment recommended — high risk of progression to overt hypothyroidism. Treat as overt hypothyroidism.

Setting: GP initiate therapy

Monitoring

Baseline

TSH, FT4, anti-TPO, FBC, lipids, CK. Document cardiac history and risk factors before starting therapy.

6–8 weeks

Re-check TSH after initiation or dose change. Adjust by 12.5–25 µg. Repeat in further 6–8 weeks if not at target.

3–6 months

TSH stable at target → reduce to 6-monthly monitoring. Reassess symptoms, weight, and adherence.

Annual

TSH annually once stable. Lipid profile — recheck if hyperlipidaemia at diagnosis (should improve). Assess for complications of overtreatment (AF, osteoporosis).

ℹ️

Brand switching: If a patient is well controlled on a specific brand (Oroxine®, Eutroxsig®, generic), advise pharmacy to avoid substitution without clinical review. Different levothyroxine formulations may have minor bioavailability differences that can perturb TSH.

Special Populations

🤰 Pregnancy

Levothyroxine dose

Most women on levothyroxine require a 25–50 % dose increase (approximately 2 additional tablets per week) as early as 4–6 weeks gestation due to increased TBG, hCG-mediated thyroid stimulation, and placental deiodinase activity. Increase dose immediately upon pregnancy confirmation — do not wait for TSH result.

TSH targets

Trimester-specific reference ranges recommended (lab-specific). If unavailable: T1 <2.5 mIU/L, T2 <3.0 mIU/L, T3 <3.5 mIU/L. Check TSH every 4 weeks in the first half of pregnancy, then at least once per trimester.

Post-partum

Reduce levothyroxine to pre-pregnancy dose immediately after delivery. Re-check TSH at 6 weeks post-partum. Monitor for post-partum thyroiditis (hyperthyroid phase → hypothyroid phase) in TPO-positive women.

👶 Paediatrics

Congenital hypothyroidism

Diagnosed via Australian Newborn Bloodspot Screening (heel-prick TSH at 48–72 hours). Initiate levothyroxine within 1–2 weeks of confirmation — delay impairs neurodevelopment. Dose: 10–15 µg/kg/day in neonates. Target T4 in upper half of reference range during the first 3 years of life. TSH target: 0.5–2.0 mIU/L.

Acquired hypothyroidism

Usually Hashimoto's. Dose: 4–6 µg/kg/day (1–5 yr), 2–4 µg/kg/day (>5 yr). Monitor growth velocity (height, weight) and bone age in addition to TSH. Reassess need for ongoing treatment after linear growth completion (late teens) — some mild cases may not require lifelong replacement.

👴 Elderly (≥65 years)

Starting dose

Begin at 25–50 µg/day. Titrate by 12.5–25 µg every 4–6 weeks. Full replacement doses may precipitate angina, myocardial infarction, or atrial fibrillation.

TSH target

Accept a higher target TSH (up to 5–6 mIU/L) in frail elderly patients to avoid overtreatment. The upper reference limit of TSH rises naturally with age — TSH of 5–7 may be physiological in octogenarians. Avoid suppressing TSH <0.4 mIU/L — increased risk of AF and fractures.

🫘 Renal Impairment

Dose adjustment

No dose adjustment required. Levothyroxine is hepatically metabolised with negligible renal clearance. However, non-thyroidal illness syndrome (euthyroid sick) is common in CKD and dialysis patients, making biochemical interpretation challenging. Consult endocrinology if uncertain.

🫁 Hepatic Impairment

Dose adjustment

No formal dose adjustment required. However, severe liver disease may impair peripheral T4-to-T3 conversion. Monitor FT3 if symptoms persist. TBG levels may be altered in cirrhosis (decreased) or hepatitis (increased), affecting total T4 but not FT4.

🛡️ Immunocompromised / Oncology

Checkpoint inhibitor thyroiditis

PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, atezolizumab) cause thyroiditis in 5–20 % of patients, often progressing to permanent hypothyroidism. Monitor TSH every 4–6 weeks during immunotherapy. Initiate levothyroxine if TSH rises above 10 mIU/L or symptomatic. Prior to thyroiditis, a transient thyrotoxic phase may occur — do not treat with anti-thyroid drugs (it is destructive, not overproduction).

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Autoimmune thyroid disease, including Hashimoto's thyroiditis, occurs in Aboriginal and Torres Strait Islander peoples, though population-level prevalence data are limited. Several barriers to diagnosis and management exist that must be addressed through culturally safe, community-centred care.

Testing access

Pathology services are limited in many remote and very remote communities. Point-of-care or fly-in pathology collection should be supported. Telehealth endocrinology consultation via RFDS or MBS-funded telehealth (MBS Items 91822–91825) can facilitate timely review.

Medication access

Levothyroxine is a PBS General Benefit but requires consistent supply and refrigeration in hot climates (stability reduces above 25 °C). Remote Area Aboriginal Health Services (Section 100) can access PBS medicines via Remote Area Aboriginal Health Services Supply. Ensure cold-chain management for levothyroxine storage.

Adherence support

Complex dosing instructions (empty stomach, timing with food) may be challenging. Provide clear, culturally appropriate education using Aboriginal Health Workers and Torres Strait Islander Health Practicers. Consider blister packs (Webster-pak®) and community pharmacy support (Closing the Gap PBS co-payment measure — $0 co-pay for eligible patients).

Pregnancy & maternal health

Antenatal screening for thyroid disease should be integrated into Aboriginal Community Controlled Health Organisation (ACCHO) maternal health programmes. Untreated hypothyroidism in pregnancy disproportionately impacts communities with limited access to early antenatal care.

Comorbidity burden

Higher rates of diabetes, cardiovascular disease, and chronic kidney disease in Aboriginal and Torres Strait Islander communities mean hypothyroid-related dyslipidaemia and cardiovascular risk require particularly active management. Integrating thyroid function testing into chronic disease management plans (MBS Item 721) is recommended.

Iodine status

Although Australia-wide mandatory iodisation has improved status, some Aboriginal and Torres Strait Islander communities — particularly in very remote areas — may have borderline iodine adequacy. Urinary iodine monitoring in these communities should be maintained.

📚 References

1. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017;390(10101):1550–1562.
2. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):988–1028.
3. Pearce SH, Brabant G, Duntas LH, et al. 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J. 2013;2(4):215–228.
4. Alexander EK, Pearce EN, Brent GA, et al. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27(3):315–389.
5. RACGP. Red Book: Guidelines for preventive activities in general practice. 9th ed. East Melbourne: RACGP; 2018.
6. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander health performance framework. Canberra: AIHW; 2023.
7. Li Y, Teng D, Shi X, et al. Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. BMJ. 2020;369:m997. [TSH population reference data]
8. Ross DS. Diagnosis of and screening for hypothyroidism. In: UpToDate, Cooper DS (Ed). Wolters Kluwer; 2024. Accessed June 2024.
9. NHMRC. National evidence-based guideline: diagnosis, management and prevention of congenital hypothyroidism. Canberra: NHMRC; 2019.
10. Wiersinga WM, Duntas L, Fadeyev V, Nygaard B, Vanderpump MP. 2012 ETA guidelines: the use of L-T4 + L-T3 in the treatment of hypothyroidism. Eur Thyroid J. 2012;1(2):55–71.
11. Pharmaceuticals Benefits Scheme (PBS). Levothyroxine sodium. Australian Government Department of Health. Available at: pbs.gov.au. Accessed June 2024.
12. Australian Government Department of Health. National Newborn Bloodspot Screening — Congenital Hypothyroidism. Available at: www.newbornscreening.gov.au. Accessed June 2024.